Statin-induced bone morphogenetic protein (BMP) 2 expression during bone regeneration: an immunohistochemical study

Abstract

The purpose of this study was to investigate bone morphogenetic protein (BMP) 2 expression after implantation of a statin and recombinant human BMP-2 (rhBMP-2) and to compare the bone regeneration capability of these substances in the rabbit nasal bone using immunohistologic methods. Twelve adult male Japanese white rabbits (n = 12; age 12-16 weeks, weight 2.5-3.0 kg) were divided into 3 experimental groups and 1 control group. A total of 48 bone defects, 4 per rabbit, were created in the nasal bone while preserving the nasal membrane. In the experimental groups, 1 group was implanted with 10 mg of a statin dissolved in 0.2 mL water with an atelocollagen sponge (ACS); the second group was implanted with 5 microg rhBMP-2 with an ACS; and in the third group only the ACS was implanted. No material was implanted in the control group. Animals were killed at 1, 2, and 4 weeks after surgery. The parts that had been operated on were removed and prepared for histologic assessment. The expression of BMP-2 was evaluated using immunohistochemistry, and double-immunostaining for BMP-2 and Ki-67 was observed by fluorescent microscopy. No significant differences were observed between the statin/ACS group and rhBMP-2/ACS group at 1, 2, and 4 weeks after surgery. The number of cells which stained positively for BMP-2 increased significantly in both of the implanted groups compared with the control group (P < .0001). The positive fluorescent double-immunostaining for BMP-2 and Ki-67 was similar in both implanted groups. This study suggests that statin/ACS implants show BMP-2 expression and osteoinductive activity that is similar to those of rhBMP-2/ACS implants.